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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21

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Author(s):
Han, Myoung Sook [1] ; Perry, Rachel J. [2, 3] ; Camporez, Joao-Paulo [2, 4] ; Scherer, Philipp E. [5, 6, 7] ; Shulman, Gerald I. [2, 3] ; Gao, Guangping [8] ; Davis, Roger J. [1]
Total Authors: 7
Affiliation:
[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 - USA
[2] Yale Sch Med, Dept Internal Med, New Haven, CT 06520 - USA
[3] Yale Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 - USA
[4] Univ Sao Paulo, Dept Physiol, Ribeirao Preto Sch Med, BR-05508000 Sao Paulo - Brazil
[5] Univ Texas Southwestern Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 - USA
[6] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 - USA
[7] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 - USA
[8] Univ Massachusetts, Sch Med, Horae Gene Therapy Ctr, Worcester, MA 01605 - USA
Total Affiliations: 8
Document type: Journal article
Source: GENES & DEVELOPMENT; v. 35, n. 1-2, p. 133-146, JAN 1 2021.
Web of Science Citations: 0
Abstract

The cJun NH2-terminal kinase (JNK) signaling pathway is activated by metabolic stress and promotes the development of metabolic syndrome, including hyperglycemia, hyperlipidemia, and insulin resistance. This integrated physiological response involves cross-talk between different organs. Here we demonstrate that JNK signaling in adipocytes causes an increased circulating concentration of the hepatokine fibroblast growth factor 21 (FGF21) that regulates systemic metabolism. The mechanism of organ crosstalk is mediated by a feed-forward regulatory loop caused by JNK-regulated FGF21 autocrine signaling in adipocytes that promotes increased expression of the adipokine adiponectin and subsequent hepatic expression of the hormone FGF21. The mechanism of organ cross-talk places circulating adiponectin downstream of autocrine FGF21 expressed by adipocytes and upstream of endocrine FGF21 expressed by hepatocytes. This regulatory loop represents a novel signaling paradigm that connects autocrine and endocrine signaling modes of the same hormone in different tissues. (AU)

FAPESP's process: 18/04956-5 - Impact of the estrogen receptor alpha on Non-Alcoholic Fatty Liver Disease and energetic metabolism of the liver
Grantee:João Paulo Gabriel Camporez
Support Opportunities: Research Grants - Young Investigators Grants